Measurement of outflow facility using iPerfusion

Elevated intraocular pressure (IOP) is the predominant risk factor for glaucoma, and reducing IOP is the only successful strategy to prevent further glaucomatous vision loss. IOP is determined by the balance between the rates of aqueous humour secretion and outflow, and a pathological reduction in the hydraulic conductance of outflow, known as outflow facility, is responsible for IOP elevation in glaucoma. Mouse models are often used to investigate the mechanisms controlling outflow facility, but the diminutive size of the mouse eye makes measurement of outflow technically challenging. In this study, we present a new approach to measure and analyse outflow facility using iPerfusion™, which incorporates an actuated pressure reservoir, thermal flow sensor, differential pressure measurement and an automated computerised interface. In enucleated eyes from C57BL/6J mice, the flow-pressure relationship is highly non-linear and is well represented by an empirical power law model that describes the pressure dependence of outflow facility. At zero pressure, the measured flow is indistinguishable from zero, confirming the absence of any significant pressure independent flow in enucleated eyes. Comparison with the commonly used 2-parameter linear outflow model reveals that inappropriate application of a linear fit to a non-linear flow-pressure relationship introduces considerable errors in the estimation of outflow facility and leads to the false impression of pressure-independent outflow. Data from a population of enucleated eyes from C57BL/6J mice show that outflow facility is best described by a lognormal distribution, with 6-fold variability between individuals, but with relatively tight correlation of facility between fellow eyes. iPerfusion represents a platform technology to accurately and robustly characterise the flow-pressure relationship in enucleated mouse eyes for the purpose of glaucoma research and with minor modifications, may be applied in vivo to mice, as well as to eyes from other species or different biofluidic systems

An evolutionary approach to the delimitation of labour market areas: an empirical application for Chile

An evolutionary approach to the delimitation of labour market areas: an empirical application for Chile. Spatial Economic Analysis. Labour market areas (LMAs) are argued to represent a more appropriate policy framework than administrative units for the analysis of spatial labour market activity. This article develops LMAs for Chile by applying an evolutionary computation approach. This innovative approach defines LMAs through an optimization process by maximization of internal cohesion, subject to restrictions of minimum levels of self-containment and population. To evaluate the appropriateness of the LMAs, comparative analyses are performed between alternative delimitations based on different parameter configurations of the proposed method versus administrative boundaries and the most widely used method for official LMA delimitation, the travel-to-work areas method

CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-value <0.05). Given the role of CR1 in host defense, our findings suggest that Sl 2 and McC(b) have arisen to confer a selective advantage against infectious disease that, in view of these case-control study data, was not solely Plasmodium falciparum malaria. Factors underlying the lack of association between Sl 2 and McC(b) with severe malaria may involve variation in CR1 expression levels

Student and staff perceptions and experiences of the introduction of Objective Structured Practical Examinations: A pilot study

Background. The Objective Structured Practical Examination (OSPE) is widely recognised as one of the more objective methods of assessing practical skills in healthcare programmes, including undergraduate physiotherapy curricula.Objectives. To obtain feedback from both students and staff who were involved in the introduction of an OSPE in 2011, in order to refine and standardise the format throughout the curriculum.Methods. A qualitative research design was used. Data were gathered through a questionnaire with semi-structured open-ended items and focus group discussion. Participants were all third-year undergraduate physiotherapy students (N=47) and all staff members (N=10) in the 2011 academic year who were exposed to the OSPE format or were involved in the first OSPE.Results. The main concerns raised by both students and staff were: (i) pressure due to time constraints and how this might affect student performance; and (ii) the question of objectivity during the assessment. However, their initial concerns changed as they experienced the OSPE in a more positive manner owing to the structure and objectivity of the process of implementing the OSPE.Conclusion. While both students and staff reported positive experiences, the challenges that emerged provided valuable insight in terms of refining the OSPE format in this undergraduate physiotherapy department

The Test Your Memory for Mild Cognitive Impairment (TYM-MCI)

BACKGROUND: To validate a short cognitive test: the Test Your Memory for Mild Cognitive Impairment (TYM-MCI) in the diagnosis of patients with amnestic mild cognitive impairment or mild Alzheimer’s disease (aMCI/AD). METHODS: Two hundred and two patients with mild memory problems were recruited. All had ‘passed’ the Mini-Mental State Examination (MMSE). Patients completed the TYM-MCI, the Test Your Memory test (TYM), MMSE and revised Addenbrooke’s Cognitive Examination (ACE-R), had a neurological examination, clinical diagnostics and multidisciplinary team review. RESULTS: As a single test, the TYM-MCI performed as well as the ACE-R in the distinction of patients with aMCI/AD from patients with subjective memory impairment with a sensitivity of 0.79 and specificity of 0.91. Used in combination with the ACE-R, it provided additional value and identified almost all cases of aMCI/AD. The TYM-MCI correctly classified most patients who had equivocal ACE-R scores. Integrated discriminant improvement analysis showed that the TYM-MCI added value to the conventional memory assessment. Patients initially diagnosed as unknown or with subjective memory impairment who were later rediagnosed with aMCI/AD scored poorly on their original TYM-MCI. CONCLUSION: The TYM-MCI is a powerful short cognitive test that examines verbal and visual recall and is a valuable addition to the assessment of patients with aMCI/AD. It is simple and cheap to administer and requires minimal staff time and training.JBR was supported by the Wellcome Trust (103838)

Pre-main-sequence isochrones - III: The Cluster Collaboration isochrone server

We present an isochrone server for semi-empirical pre-main-sequence model isochrones in the following systems: Johnson–Cousins, Sloan Digital Sky Survey, Two-Micron All-Sky Survey, Isaac Newton Telescope (INT) Wide-Field Camera and INT Photometric Hα Survey (IPHAS)/UV-Excess Survey (UVEX). The server can be accessed via the Cluster Collaboration webpage http://www.astro.ex.ac.uk/people/timn/isochrones/. To achieve this, we have used the observed colours of member stars in young clusters with well-established age, distance and reddening to create fiducial loci in the colour–magnitude diagram. These empirical sequences have been used to quantify the discrepancy between the models and data arising from uncertainties in both the interior and atmospheric models, resulting in tables of semi-empirical bolometric corrections (BCs) in the various photometric systems. The model isochrones made available through the server are based on existing stellar interior models coupled with our newly derived semi-empirical BCs. As part of this analysis, we also present new cluster parameters for both the Pleiades and Praesepe, yielding ages of 135+20−11 and 665+14−7Myr as well as distances of 132 ± 2 and 184 ± 2 pc, respectively (statistical uncertainty only)

Pre-main-sequence isochrones - III. The cluster collaboration isochrone server

We present an isochrone server for semi-empirical pre-main-sequence model isochrones in the following systems: Johnson-Cousins, Sloan Digital Sky Survey, Two-Micron All-Sky Survey, Isaac Newton Telescope (INT) Wide-Field Camera and INT Photometric Ha Survey (IPHAS)/UV-Excess Survey (UVEX). The server can be accessed via the Cluster Collaboration webpage http://www.astro.ex.ac.uk/people/timn/isochrones/. To achieve this, we have used the observed colours ofmember stars in young clusters with well-established age, distance and reddening to create fiducial loci in the colour-magnitude diagram. These empirical sequences have been used to quantify the discrepancy between the models and data arising from uncertainties in both the interior and atmospheric models, resulting in tables of semi-empirical bolometric corrections (BCs) in the various photometric systems. The model isochrones made available through the server are based on existing stellar interior models coupled with our newly derived semi-empirical BCs. As part of this analysis, we also present new cluster parameters for both the Pleiades and Praesepe, yielding ages of 135+20 -11 and 665+14 -7 Myr as well as distances of 132 ± 2 and 184 ± 2 pc, respectively (statistical uncertainty only).JMR is funded by a UK Science and Technology Facilities Council (STFC) studentship. EEM acknowledges support from the National Science Foundation (NSF) Award AST-1008908. The authors would like to thank Emanuele Tognelli for the updated set of Pisa models and John Stauffer for sharing his catalogue of Kron photometric measurements of Pleiades members. The authors would also like to thank the referee for comments which have vastly improved the clarity of the manuscript. This research has made use of data obtained at the Isaac Newton Telescope, which is operated on the island of La Palma by the Isaac Newton Group (ING) in the Spanish Observatorio del Roque de los Muchachos of the Institutio de Astrofisica de Canarias. This research has made use of archival data products from the Two-Micron All-Sky Survey (2MASS), which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center, funded by the National Aeronautics and Space Administration (NASA) and the National Science Foundation. This research has made use of public data from the SDSS. Funding for the SDSS was provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, the US Department of Energy, the National Aeronautics and Space Administration, the Japanese Monbukagakusho, the Max Planck Society and the Higher Education Funding Council for England. The SDSS was managed by the Astrophysical Research Consortium for the Participating Institutions

Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis

Increased rates of brain atrophy measured from serial magnetic resonance imaging precede symptom onset in Alzheimer's disease and may be useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. Fifty-two healthy individuals (72.3 ± 6.9 years) from Australian Imaging, Biomarkers and Lifestyle Study of Aging had serial (0, 18 m, 36 m) magnetic resonance imaging, (0, 18 m) Pittsburgh compound B positron emission tomography, and clinical assessments. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over 3 years, rates of whole brain atrophy (p < 0.001), left and right hippocampal atrophy (p = 0.001, p = 0.023), and ventricular expansion (p < 0.001) were associated with baseline β-amyloid load. Whole brain atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p = 0.003). Acceleration of left hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p < 0.02). We provide evidence that rates of atrophy are associated with both baseline β-amyloid load and accumulation, and that there is presymptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the presymptomatic phase

Association between Knops blood group polymorphisms and susceptibility to malaria in an endemic area of the Brazilian Amazon

Complement receptor 1 (CR1) gene polymorphisms that are associated with Knops blood group antigens may influence the binding of Plasmodium parasites to erythrocytes, thereby affecting susceptibility to malaria. The aim of this study was to evaluate the genotype and allele and haplotype frequencies of single-nucleotide polymorphisms (SNPs) of Knops blood group antigens and examine their association with susceptibility to malaria in an endemic area of Brazil. One hundred and twenty-six individuals from the Brazilian Amazon were studied. The CR1-genomic fragment was amplified by PCR and six SNPs and haplotypes were identified after DNA sequence analysis. Allele and haplotype frequencies revealed that the Knb allele and H8 haplotype were possibly associated with susceptibility to Plasmodium falciparum. The odds ratios were reasonably high, suggesting a potentially important association between two Knops blood antigens (Knb and KAM+) that confer susceptibility to P. falciparum in individuals from the Brazilian Amazon